Osteoarthritis (OA) is a degenerative disease of the articular cartilage affecting millions of people worldwide. As no current treatment can fully and consistently restore normal joint function to patients afflicted with OA, there is a significant clinical need for alternative therapies for cartilage regeneration. Many approaches to the tissue engineering of articular cartilage involve the use of cells in combination with soluble bioactive factors and biomaterials that may provide specific microenvironmental cues for chondrogenic induction. Mesenchymal stem cells (MSCs) from bone marrow have been shown to be a promising cell source for these cartilage tissue engineering strategies, as they can be expanded in culture without losing multipotency, and can differentiate into many cell types of the connective tissue lineage including chondrocytes under appropriate conditions. Specifically, two important factors for the in vitro chondrogenic induction of MSCs are high initial cell density and exposure to transforming growth factor β (TGF-β).
Several in vitro culture methods have been developed for MSC chondrogenesis, including aggregate or pellet culture, micromass culture, and self-assembling cell sheet systems. These culture systems take advantage of the abundant cell-cell interactions that occur in 3D high density culture, without the potential interference of a biomaterial scaffold. In particular, self-assembling cell sheets show promise for use in cartilage tissue engineering applications, as they may form larger constructs with much greater surface areas and volumes than aggregates or tiny micromass cultures. Unlike spherical cell aggregates, which are limited in size by the diffusion distance of nutrients into the center of the sphere, flat sheets of various dimensions can be formed without necessitating a proportional increase in construct thickness, enabling nutrient diffusion to all regions of the tissue. Upon surgical evaluation, chondral defects in the knee have an area of at least 0.5 cm2, with over a third of the defects having areas of at least 1 cm2. Self-assembling sheets could be clinically practical for the treatment of these defects, as sheets of the appropriate size could be formed and then implanted into a defect as an intact piece. This is in contrast to smaller cell constructs, which may not be as readily applied for the clinical treatment of cartilage defects since a number of constructs would be required to fill a single lesion. It may be difficult to localize multiple constructs to a defect, and in order to repair the damaged cartilage, the individual cell constructs would have to integrate with each other as well as with the surrounding host tissue.